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Assessment of tailor-made HPMC-based matrix minitablets comprising a weakly basic drug compound
Stefanie Siepe1, Barbara Lueckel, Andrea Kramer
1Novartis Pharma AG, Technical R&D, Basel, Switzerland. stefanie.siepe@novartis.com
Drug Development and Industrial Pharmacy
|January 25, 2008
Summary
pH modifiers like fumaric acid enhance dipyridamole release from HPMC matrix minitablets. Fumaric acid showed a more pronounced effect on microenvironmental pH (pHM) control for sustained drug delivery.
Area of Science:
- Pharmaceutical technology
- Drug delivery systems
Background:
- Developing pH-controlled drug delivery systems is crucial for optimizing the release of weakly basic drugs like dipyridamole.
- Hydroxypropyl methylcellulose (HPMC) based matrix systems offer potential for controlled release applications.
Purpose of the Study:
- To develop and characterize tailor-made, pH-controlled matrix minitablets for the drug dipyridamole using different HPMC types.
- To investigate the impact of incorporated pH modifiers (fumaric acid, succinic acid) on drug release and microenvironmental pH (pHM).
Main Methods:
- Formulation of matrix minitablets using various HPMC grades and incorporating dipyridamole with fumaric or succinic acid.
- In vitro assessment of drug release, acid release, and microenvironmental pH (pHM) at different time points.
- Evaluation of the influence of HPMC type and pH modifiers on release kinetics.
Main Results:
- Incorporation of fumaric and succinic acid significantly enhanced dipyridamole release at pH 6.8.
- Fumaric acid demonstrated a more pronounced and prolonged alteration of the microenvironmental pH (pHM).
- Minitablets formulated with Methocel K100LV exhibited simultaneous release of dipyridamole and fumaric acid, maintaining a consistently low pHM.
Conclusions:
- pH modifiers, particularly fumaric acid, are effective in controlling the microenvironmental pH and enhancing the release of dipyridamole from HPMC matrix minitablets.
- The choice of HPMC grade and pH modifier can be tailored to achieve desired drug release profiles for improved therapeutic outcomes.
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